Short-Wavelength Light Sensitivity of Circadian, Pupillary, and Visual Awareness in Humans Lacking an Outer Retina

Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London W6 8RF, United Kingdom.
Current Biology (Impact Factor: 9.92). 01/2008; 17(24):2122-8. DOI: 10.1016/j.cub.2007.11.034
Source: PubMed

ABSTRACT As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus ( approximately 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light.

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Available from: Kevin Gregory-Evans, Aug 30, 2015
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    • "IpRGCs project to brain areas associated with non-imageforming functions, such as the SCN for circadian photoentrainment (Hattar et al., 2003; Ruby et al., 2002) and the olivary pretectal nucleus (OPN) for controlling pupil size (Clarke, Zhang, & Gamlin, 2003; Hattar et al., 2002; Lucas et al., 2003). IpRGCs also project to the LGN (Berson, 2003; Dacey et al., 2005) and may contribute to image-forming processes (Barrionuevo & Cao, 2014; Brown et al., 2012; Horiguchi, Winawer, Dougherty, & Wandell, 2013; Zaidi et al., 2007). "
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    ABSTRACT: Intrinsically photosensitive retinal ganglion cells (ipRGCs) can respond to light directly through self-contained photopigment, melanopsin. IpRGCs also receive inputs from rods and cones. Thus, studying ipRGC functions requires a novel photostimulating method that can account for all of the photoreceptor inputs. Here, we introduce an inexpensive LED-based five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones and melanopsin-containing ipRGCs in humans at constant background photoreceptor excitation levels, a critical requirement for studying the adaptation behavior of ipRGCs with rod, cone or melanopsin input. We describe the theory and technical aspects (including optics, electronics, software and calibration) of the five-primary photostimulator. Then we present two preliminary studies using the photostimulator we have implemented to measure melanopsin-mediated pupil responses and temporal contrast sensitivity function (TCSF). The results showed that the S-cone input to pupil responses was antagonistic to the L-, M- or melanopsin inputs, consistent with an S-OFF and (L+M)-ON response property of primate ipRGCs (Dacey et al., 2005). In addition, the melanopsin-mediated TCSF had a distinctive pattern compared with L+M or S-cone mediated TCSF. Other than control individual photoreceptor excitation independently, the five-primary photostimulator has the flexibility in presenting stimuli modulating any combination of photoreceptor excitations, which allows to study the mechanisms by which ipRGCs combine various photoreceptor inputs.
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    • "The recent progress in understanding how light changes are unconsciously captured and transmitted to the circadian system (Benarroch, 2011; Foster and Hankins, 2007; Hatori and Panda, 2010) may someday help to explain the solar insolation findings in this study. Photosensitive retinal ganglion cells (pRGC) containing the pigment melanopsin mediate a broad range of non-image forming functions including circadian synchronization, melatonin suppression and alertness (Berson, 2003, Gooley et al., 2003; Zaidi et al., 2007). The intrinsic photosensitivity of pRGC is specialized to detect fluctuations in intensity of environmental light (Berson, 2003, Hatori and Panda, 2010) and the signals are sent to the circadian pacemaker in the suprachiasmatic nucleus (SCN). "
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    ABSTRACT: BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS: Recall bias for onset and family history data. CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.
    Journal of Affective Disorders 05/2014; 167C. DOI:10.1016/j.jad.2014.05.032 · 3.71 Impact Factor
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    • "In fact, the circadian clock runs free without entrainment (synchronization) to environmental signals, especially the light/dark cycle in a day. As mentioned above, parallel studies have demonstrated an important role of melanopsin in circadian entrainment [1,5,11,14]. Melanopsin-containing retinal ganglion cells detect irradiance information and transmit the photic signal to the suprachiasmatic nucleus, the circadian pacemaker, located in the hypothalamus [15]. "
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    ABSTRACT: Background In our previous studies, we found that the Ile394Thr SNP in the melanopsin gene (OPN4) was functionally associated with the pupillary light reflex. This indicates the possibility that OPN4*Ile394Thr is associated with other non-image forming responses. The aim of this study was therefore to determine whether OPN4*Ile394Thr is associated with sleep/wake timing. Methods A total of 348 healthy Japanese university students participated in this study. Scalp hair was used to genotype the Ile394Thr SNP of OPN4. Sleep habits, including bedtime, wake time and sleep duration, were assessed separately for weekdays and weekends. A total of 328 samples, including 223 samples with TT genotype, 91 with TC genotype and 14 with CC genotype, were used for statistical analysis. No significant difference in age or male/female distribution was found among the three genotype groups. Results There was no significant difference in circadian preference among the genotype groups. During weekdays, bedtime, wake time and midpoint of sleep for CC subjects were significantly later than those for TT and TC subjects. However, there was no difference between TT and TC subjects in any of their sleep habits. During weekends, bedtime of CC subjects was significantly later than those of TT and TC subjects, and the midpoint of sleep of CC subjects was significantly later than that of TC subjects. Conclusions Our findings demonstrated that OPN4*Ile394Thr is associated with sleep/wake timing. We also found that the sleep/wake timing of subjects with the CC genotype was later than that of subjects with the TT or TC genotype.
    Journal of PHYSIOLOGICAL ANTHROPOLOGY 05/2014; 33(1):9. DOI:10.1186/1880-6805-33-9 · 1.27 Impact Factor
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